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Allele Symbol Allele Name Allele ID |
Apctm2Rak targeted mutation 2, Raju Kucherlapati MGI:3688435 |
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| Summary |
10 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 7% of tumors that develop in mutant colons injected with an adenovirus expressing cre recombinase are carcinomas
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• 71% of mutants injected with an adenovirus expressing cre recombinase in the distal colon to inactivate Apc develop distal colonic tumors as little as 6 weeks after viral administration
• rapamycin treatment of mutants with tumors results in tumor regression, with mice showing an 82% reduction in tumor size
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• 93% of tumors that develop in mutant colons injected with an adenovirus expressing cre recombinase are adenomas
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• 93% of tumors that develop in mutant colons injected with an adenovirus expressing cre recombinase are adenomas
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| colorectal cancer | DOID:9256 |
OMIM:114500 |
J:156532 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 36% of tumors that develop in mutant colons injected with an adenovirus expressing cre recombinase are carcinomas
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• 20% of mutants injected with an adenovirus expressing cre recombinase in the distal colon to inactivate Apc exhibit spontaneous gross liver metastases starting 24 weeks after adenoviral injection; these lesions are adenocarcinomas
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• 96% of mutants injected with an adenovirus expressing cre recombinase in the distal colon to inactivate Apc develop distal colonic tumors as little as 3 weeks after viral administration
• rapamycin treatment of mutants with tumors does not result in tumor regression
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• 64% of tumors that develop in mutant colons injected with an adenovirus expressing cre recombinase are adenomas
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• 64% of tumors that develop in mutant colons injected with an adenovirus expressing cre recombinase are adenomas
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| colorectal cancer | DOID:9256 |
OMIM:114500 |
J:156532 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice develop colonic tumors, characterized as adenomas with low-grade dysplasia
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• mice show slightly longer survival than conditional mice carrying the Krastm4Tyj allele
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• mice develop colonic tumors, characterized as adenomas with low-grade dysplasia
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| colorectal cancer | DOID:9256 |
OMIM:114500 |
J:276349 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice develop colonic tumors, characterized as adenomas with low-grade dysplasia
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• mice show 100% lethality before 150 days of age
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• mice develop colonic tumors, characterized as adenomas with low-grade dysplasia
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| colorectal cancer | DOID:9256 |
OMIM:114500 |
J:276349 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• survival is shorter than either single conditional mutant; mice can survive up to 32 weeks but most have to be euthanized at 24-26 weeks of age
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• all mice develop pancreatic neoplasms between 16 and 24 weeks
• 100% of mice exhibit large cystic pancreata which are mucinous cystadenomas, characterized by the presence of unilocular megacystic lesions with mucoid/watery cyst content, and nodules or peripheral calcification on the cyst wall resembling human mucinous cystic neoplasm
• mucinous cystic neoplasms become malignant pancreatic cancer with nuclear anaplastic features, and show stomach, duodenal or intestinal invasion or liver or lung metastasis, consistent with aggressive pancreatic cystic adenocarcinoma
• 6 week old mice treated with the Wnt inhibitor IWP-2 for 12 weeks show a reduction of or absence of hypertrophic pancreas with cysts
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• tumors exhibit a high incidence of metastasis and invasion
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• 100% of mice exhibit large cystic pancreata which are mucinous cystadenomas
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• all mice develop pancreatic neoplasms between 16 and 24 weeks
• 100% of mice exhibit large cystic pancreata which are mucinous cystadenomas, characterized by the presence of unilocular megacystic lesions with mucoid/watery cyst content, and nodules or peripheral calcification on the cyst wall resembling human mucinous cystic neoplasm
• mucinous cystic neoplasms become malignant pancreatic cancer with nuclear anaplastic features, and show stomach, duodenal or intestinal invasion or liver or lung metastasis, consistent with aggressive pancreatic cystic adenocarcinoma
• 6 week old mice treated with the Wnt inhibitor IWP-2 for 12 weeks show a reduction of or absence of hypertrophic pancreas with cysts
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• cystic fluid of the pancreata shows the induction of the following cytokines: FasL, soluble tumor necrosis factor receptor 1, IL-1beta, IL-6, macrophage inflammatory protein 1gamma, keratinocyte chemoattractant and monocyte chemoattractant protein 1
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• cystic fluid of the pancreata shows the induction of the following cytokines: FasL, soluble tumor necrosis factor receptor 1, IL-1beta, IL-6, macrophage inflammatory protein 1gamma, keratinocyte chemoattractant and monocyte chemoattractant protein 1
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pancreatic mucinous cystadenoma | DOID:7235 | J:234310 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• maturation of the prenatal pancreas is disrupted
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• altered gastrointestinal development
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Stunted growth, short whiskers, sparse hair coat and abnormal tooth development in the Apctm2Rak/Apctm2Rak Tg(KRT14-cre)8Brn/0 mouse
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• some pups have died by P8-10 and none survive to weaning; time of death is variable with some dying within 1-2 days of birth, while some survive almost to weaning
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• maxillary incisors are often absent or underdeveloped
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• initiation of ectopic tooth buds is evident by E15.5
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• at time of death, animals are toothless
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• at E17.5-18.5 mutants display a patch of dark pigmentation on the forehead
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• external ears or pinnae are shriveled in appearance
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• external ears or pinnae are pigmented compared to littermates
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• by P8-10, mutant pups are considerably smaller than wild-type
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• mutants start to lose weight from P10 onwards
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• mutants show aberrant proliferation and differentiation of keratinocytes leading to massive squamous metaplasia, rather than forming medullary or cortical thymic epithelial cells
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• in skin, proliferating cells are observed in cells in bulbs at base of hair cells and in bulb-like structures budding from outer root sheaths of existing hair follicles
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• maxillary incisors are often absent or underdeveloped
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• initiation of ectopic tooth buds is evident by E15.5
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• at time of death, animals are toothless
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• at E17.5-18.5 mutants display a patch of dark pigmentation on the forehead
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• external ears or pinnae are shriveled in appearance
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• external ears or pinnae are pigmented compared to littermates
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• hyperplasia in salivary gland squamous epithelium is observed
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• at P12-17, thymi frequently contain black deposits within the tissue
• in more severely affected mutants, by P3, distinct thymic epithelial compartments are lost as well as most lymphocytes
• at P10-13, thymus consists of numerous enlarged Hassall's corpuscle-like structures surrounding large keratin deposits, and show large numbers of infiltrating neutrophils and macrophages in response to keratins
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• numerous enlarged Hassall's corpuscle-like structures surrounding large keratin deposits
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• thymi are inconspicuous and small for pups' age; this is evident by P3
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• no thymocytes are detectable at P10-13
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• hyperplasia in squamous epithelium is observed
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• hyperplasia in salivary gland squamous epithelium is observed
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• stomach is small at time of death, and contains no solid food
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• at E17.5-18.5 mutants display patch of dark pigmentation on forehead and a dark median line running caudally from head to tail
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• at E17.5-18.5 mutants display a patch of dark pigmentation on the forehead
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• external ears or pinnae are pigmented compared to littermates
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• at P12-17, thymi frequently contain black deposits within the tissue
• in more severely affected mutants, by P3, distinct thymic epithelial compartments are lost as well as most lymphocytes
• at P10-13, thymus consists of numerous enlarged Hassall's corpuscle-like structures surrounding large keratin deposits, and show large numbers of infiltrating neutrophils and macrophages in response to keratins
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• numerous enlarged Hassall's corpuscle-like structures surrounding large keratin deposits
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• thymi are inconspicuous and small for pups' age; this is evident by P3
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• no thymocytes are detectable at P10-13
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• at P12-17, thymi frequently contain black deposits within the tissue
• in more severely affected mutants, by P3, distinct thymic epithelial compartments are lost as well as most lymphocytes
• at P10-13, thymus consists of numerous enlarged Hassall's corpuscle-like structures surrounding large keratin deposits, and show large numbers of infiltrating neutrophils and macrophages in response to keratins
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• numerous enlarged Hassall's corpuscle-like structures surrounding large keratin deposits
|
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• thymi are inconspicuous and small for pups' age; this is evident by P3
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• no thymocytes are detectable at P10-13
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• maxillary incisors are often absent or underdeveloped
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• initiation of ectopic tooth buds is evident by E15.5
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• at time of death, animals are toothless
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• hyperplasia in squamous epithelium of cornea occurs
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• by P17, animals hardly keep eyes open
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• external ears or pinnae are shriveled in appearance
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• external ears or pinnae are pigmented compared to littermates
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• mutants show aberrant proliferation and differentiation of keratinocytes leading to massive squamous metaplasia, rather than forming medullary or cortical thymic epithelial cells
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• at ~P8, mutants are hairless while normal littermates have a smooth thin coat
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• around P10-12, mice display short, shaggy coats
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• at P3, follicles are often irregularly spaced and seen as disoriented and clamped invaginations that become more noticeable at P12
• clusters of dysplastic follicular structures are frequently observed throughout the epidermis, while other regions display gaps with no follicles
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• bulbs are often bent and irregularly angled to one another, with variable size and location
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• ectopic hair follicle morphogenesis is observed in epithelium of cornea, oral, salivary, and Harderian glands
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• at P12, some hair follicles are not properly formed or shorter than normal
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• around P10-12, mutants display short and misshapen vibrissae
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• ridged skin regions look scaly
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• at P17, development of thick ridges in the skin around the ears, eyelids, forehead, nose and paws becomes noticeable
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• mutants have wrinkled skin at P8
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• at E17.5-18.5 mutants display patch of dark pigmentation on forehead and a dark median line running caudally from head to tail
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• at E17.5-18.5 mutants display a patch of dark pigmentation on the forehead
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• external ears or pinnae are pigmented compared to littermates
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• visible gross tumors are observed by 10 weeks of age with no increase in incidence up to 20 weeks in about 20% of animals; two types of lesions (microadenomas and adenomas) are identifiable microscopically
• both lesion types are overrepresented in the distal colon; microadenomas are present in proximal colon as well
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• over 60% of mice receiving dextran sodium sulfate (DSS) for 7 days starting at 10 weeks of age have grossly visible adenomatous lesions in the colon with over 70% of the lesions found in the distal colon; mortality is observed in 55% of animals within 4 days of end of treatment, with remainder of treated mice surviving until end point of study at 15 weeks
• about 50% of mice receiving DSS for 5 days starting at 10 weeks of age develop visible tumors by 20 weeks of age with all lesions in the distal colon; mortality is observed in 20% of animals within 4 days of end of treatment, with remainder of treated mice surviving until end point of study at 15 weeks
• some microadenomas are observed in the cecum after DSS treatment
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| N |
• no differences in body weight are observed relative to wild-type even when animals have tumors
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• over 60% of mice receiving dextran sodium sulfate (DSS) for 7 days starting at 10 weeks of age have grossly visible adenomatous lesions in the colon with over 70% of the lesions found in the distal colon; mortality is observed in 55% of animals within 4 days of end of treatment, with remainder of treated mice surviving until end point of study at 15 weeks
• about 50% of mice receiving DSS for 5 days starting at 10 weeks of age develop visible tumors by 20 weeks of age with all lesions in the distal colon; mortality is observed in 20% of animals within 4 days of end of treatment, with remainder of treated mice surviving until end point of study at 15 weeks
• some microadenomas are observed in the cecum after DSS treatment
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• some adenomatous polyps are identifiable as sessile or pedunculated
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• visible gross tumors are observed by 10 weeks of age with no increase in incidence up to 20 weeks in about 20% of animals; two types of lesions (microadenomas and adenomas) are identifiable microscopically
• both lesion types are overrepresented in the distal colon; microadenomas are present in proximal colon as well
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• some mice with tumors produce bloody stool
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• hematocrit of mice is 37% vs 48% in wild-type
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice are able to survive up to 6 weeks of age
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• body weights are reduced by 12.8% at 3 weeks and by 20% at 6 weeks
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• raised lesions are observed in large intestine at 3 and 6 weeks
• affected areas display mucosal thickening, characterized by dysplastic epithelial cells with increased nuclear to cytoplasmic ratios and increased mitotic figures typical of microadenomas
• by 6 weeks, microadenomas and adenomas are multifocally distributed throughout distal and proximal colon
• lesions exhibit cytoplasmic and nuclear accumulation of beta-catenin in dysplastic epithelial cells; proliferation of these cells is increased, and extends beyond the crypt base
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• all mice develop rectal prolapse by 3 weeks of age
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• raised lesions are observed in large intestine at 3 and 6 weeks
• affected areas display mucosal thickening, characterized by dysplastic epithelial cells with increased nuclear to cytoplasmic ratios and increased mitotic figures typical of microadenomas
• by 6 weeks, microadenomas and adenomas are multifocally distributed throughout distal and proximal colon
• lesions exhibit cytoplasmic and nuclear accumulation of beta-catenin in dysplastic epithelial cells; proliferation of these cells is increased, and extends beyond the crypt base
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• hematocrit is decreased by >40% compared to Apctm2Rak/+ Tg(Car1-cre)5Flt mutants
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/16/2024 MGI 6.23 |
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